Hydrochloric Acid → HCID 178492188, compound

HRID 510940Notes

Reaction equation

HRID 510940 reaction equation
[Cl:1][C:2]1[C:3]([CH3:36])=[C:4]([CH:22]2[CH2:25][N:24](C(OCC3C=CC=CC=3)=O)[CH2:23]2)[C:5]([O:20][CH3:21])=[C:6]([CH:8]([NH:10][C:11]2[N:19]=[CH:18][N:17]=[C:16]3[C:12]=2[N:13]=[CH:14][NH:15]3)[CH3:9])[CH:7]=1.Cl.O>CO.[Pd]>[NH:24]1[CH2:25][CH:22]([C:4]2[C:5]([O:20][CH3:21])=[C:6]([CH:8]([NH:10][C:11]3[N:19]=[CH:18][N:17]=[C:16]4[C:12]=3[N:13]=[CH:14][NH:15]4)[CH3:9])[CH:7]=[C:2]([Cl:1])[C:3]=2[CH3:36])[CH2:23]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 178492193HCID 178492193, compound

Product 1

HCID 178492188HCID 178492188, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Benzyl 3-{3-chloro-6-methoxy-2-methyl-5-[1-(9H-purin-6-ylamino)ethyl]phenyl}azetidine-1-carboxylate (255 mg, 0.503 mmol) and 5% palladium (125 mg) was combined in methanol (15 mL), to which was added 0.25 M HCl in water (5.0 mL, 1.2 mmol). The suspension was hydrogenated under balloon pressure of H2 at room temperature overnight. The suspension was filtered and concentrated to give N-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-9H-purin-6-amine. LCMS calculated for C18H22ClN6O (M+H)+: m/z=373.2. found: 373.1. The azetidine intermediate made above was combined with DIPEA (0.26 mL, 1.5 mmol) in methanol (0.5 mL)/acetonitrile (0.5 mL)/THF (0.5 mL), followed by the addition of 37% formaldehyde (0.19 mL, 2.5 mmol). The mixture was stirred at room temperature for 10 min before the addition of sodium triacetoxyborohydride (0.32 g, 1.5 mmol). The mixture was stirred at room temperature overnight, then diluted with MeOH and purified on prep-LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.05% trifluoroacetic acid, at flow rate of 30 mL/min) to afford the desired product as TFA salt. LCMS calculated for C19H24ClN6O (M+H)+: m/z=387.2. found: 387.1.

Workup

  1. filtrationThe suspension was filtered
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-7fa440ba64534e8988c0ac7067c84dd4
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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